Model-based Dose Selection for Phase III Rivaroxaban Study in Japanese Patients with Non-valvular Atrial Fibrillation
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- TANIGAWA Takahiko
- Development Clinical Pharmacology Asia, Bayer Yakuhin Ltd.
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- KANEKO Masato
- Development Clinical Pharmacology Asia, Bayer Yakuhin Ltd.
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- HASHIZUME Kensei
- Development Clinical Pharmacology Asia, Bayer Yakuhin Ltd.
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- KAJIKAWA Mariko
- Clinical Development Cardiovascular, Bayer Yakuhin Ltd.
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- UEDA Hitoshi
- Medical Scientific Liaison, Bayer Yakuhin Ltd.
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- TAJIRI Masahiro
- Clinical Development Cardiovascular, Bayer Yakuhin Ltd.
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- PAOLINI John F.
- Bayer HealthCare Pharmaceuticals
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- MUECK Wolfgang
- Development Clinical Pharmacology, Bayer HealthCare AG
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抄録
The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.<br>
収録刊行物
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 28 (1), 59-70, 2013
日本薬物動態学会